The overall goal of our research is to elucidate molecular mechanisms which are involved in the regulation of RNA synthesis in mammalian cells. To approach this goal, we are using animal viruses as agents to specifically alter cellular RNA metabolism and as model RNA synthetic systems. Infection of appropriate cells with picornaviruses results in a rapid inhibition of the initiation of RNA synthesis by RNA polymerase II. This inhibition is accomplished by a mechanism which does not result in gross alterations of either the enzyme or the template chromatin. Our future studies of this regulation will involve analysis of the expression of specific genes and specific proteins (particularly non-histone chromosomal proteins) in picornavirus infected cells. Much of the protein analysis will focus on determination of the patterns of specific modification of nuclear proteins, particularly phosphorylations. The expression and replication of influenza virus genes are related and regulated processes which involve the action of a limited number of cellular and viral components. The goal of our studies in this system is to determine the manner in which these components act and interact in infected cells. Since phosphorylation of viral proteins seems to play a role in this system, the source and significance of this modification will be explored in detail.